ASCO 2026: Adjuvant Selpercatinib in Early-Stage RET Fusion–Positive NSCLC
Posted: Friday, June 12, 2026
Adjuvant therapy with the brain-penetrant RET inhibitor selpercatinib appeared to improve event-free survival in patients with early-stage RET fusion–positive non–small cell lung cancer (NSCLC), according to Jonathan W. Goldman, MD, of the University of California, Los Angeles, and colleagues. Presented at the 2026 ASCO Annual Meeting (Abstract LBA3) and simultaneously published in The New England Journal of Medicine, their findings from the phase III LIBRETTO-432 trial further support the use of comprehensive genomic testing at diagnosis across disease stages to guide treatment decision-making.
“These data add to the body of evidence for targeted therapy, including EGFR and ALK inhibitors, in the adjuvant NSCLC setting…,” the investigators commented.
Patients with stage IB to IIIA disease who had completed definitive locoregional treatment were randomly assigned in a 1:1 ratio to receive selpercatinib or placebo twice daily for up to 3 years. Crossover to selpercatinib was allowed for those who experienced disease recurrence with placebo. Follow-up data were provided for a median of 24 and 27 months for selpercatinib and placebo, respectively.
In patients with stage II to IIIA disease (n = 109), selpercatinib seemed to significantly improve investigator-assessed event-free survival (hazard ratio [HR] = 0.172; P = .0003). Median event-free survival was not reached vs 31.8 months with selpercatinib vs placebo, respectively (4 vs 19 events). Event-free survival assessed by blinded independent central review appeared consistent with the investigator-assessed results (HR = 0.125; P = .0011). At 2 years, the event-free survival rate was 91.5% with selpercatinib vs 61.1% with placebo.
In the overall population (n = 151), the error-controlled HR for investigator-assessed event-free survival was 0.165 (P = .0002), and median event-free survival had not been reached in either arm. The safety profile of selpercatinib in the overall population was found to be consistent with that reported in the metastatic setting. The most frequently reported adverse events were increased alanine aminotransferase and aspartate aminotransferase levels. Three deaths were observed, all in the placebo arm and attributed to the study disease; no patients died during assigned study treatment.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
